The Sushi domains of GABAB receptors function as axonal targeting signals.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Barbara BiermannBernhard Bettler

Abstract

GABA(B) receptors are the G-protein-coupled receptors for GABA, the main inhibitory neurotransmitter in the brain. Two receptor subtypes, GABA(B(1a,2)) and GABA(B(1b,2)), are formed by the assembly of GABA(B1a) and GABA(B1b) subunits with GABA(B2) subunits. The GABA(B1b) subunit is a shorter isoform of the GABA(B1a) subunit lacking two N-terminal protein interaction motifs, the sushi domains. Selectively GABA(B1a) protein traffics into the axons of glutamatergic neurons, whereas both the GABA(B1a) and GABA(B1b) proteins traffic into the dendrites. The mechanism(s) and targeting signal(s) responsible for the selective trafficking of GABA(B1a) protein into axons are unknown. Here, we provide evidence that the sushi domains are axonal targeting signals that redirect GABA(B1a) protein from its default dendritic localization to axons. Specifically, we show that mutations in the sushi domains preventing protein interactions preclude axonal localization of GABA(B1a). When fused to CD8alpha, the sushi domains polarize this uniformly distributed protein to axons. Likewise, when fused to mGluR1a the sushi domains redirect this somatodendritic protein to axons, showing that the sushi domains can override dendritic targeting information in...Continue Reading

Citations

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